Senefol - informacja o leku

23 January 2024

Senefol – product information

SUMMARY OF PRODUCT CHARACTERISTICS

PRODUCT NAME

SENEFOL, 7.5 mg of hydroxyanthracene derivatives, expressed as sennoside B, tablets

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 300 mg of Cassia senna L. (C. acutifolia Delile), fructus and/or Cassia angustifolia Vahl, fructus and/or Cassia senna L (C. acutifolia Delile) and/or Cassia angustifolia Vahl., foliolum (senna leaflet and fruit), equivalent to 7.5 mg of hydroxyanthracene derivatives, expressed as sennoside B.

See below for full list of excipients.

PHARMACEUTICAL FORM

Tablet

CLINICAL PARTICULARS

Indications

Herbal medicine used in emergency treatment of constipation.

For bowel cleansing preceding diagnostic tests and surgery.

Posology and method of administration

Posology:

Maximum daily dose: 4 tablets.

The maximum daily dose of hydroxyanthracene glycosides is 30 mg, equivalent to 4 tablets.

The appropriate personal dose is the lowest dose required for soft stool.

Adolescents over 12 years, adults: 2-4 tablets before sleep. Wash down with large quantity of water.

Considering varying individual sensitivity, dosing should begin with the lowest dose (1 tablet), to be increased if needed to determine the effective dose. The laxative effect takes place after 8-12 hours, if none is observed the next dose should be taken after 12 hours.

Children

Do not use in children under 12 years (see: 4.3).

Method of administration

Oral

Duration of use

2-3 times a week is usually sufficient to obtain the therapeutic effect.

Usage longer than 1-2 weeks should be decided on by a doctor.

If symptoms persist during use, consult a doctor or pharmacist.

Contraindications

Hypersensitivity to active ingredient. Bowel obstruction, intestinal stenosis or atony, appendicitis, inflammatory bowel disease such as Crohn's disease, ulcerative colitis, abdominal pain of unknown origin, dehydration and loss of electrolytes. Do not use in children under 12 years.

Special warnings and precautions for use

Not intended for long-term use. Patients should be informed that use longer than 1-2 weeks is decided by a doctor. Use of laxatives for longer than recommended can disrupt bowel function and cause dependency. Products containing hydroxyanthracene glycosides should be prescribed only if proper bowel movement cannot be attained through change of diet.

Patients taking cardiac glycosides, antiarrhythmic medication, QT-prolonging drugs, diuretics, corticosteroids or liquorice root should consult a doctor before taking hydroxyanthracene glycosides. As with laxatives, products containing hydroxyanthracene glycosides should not be taken by patients with fecal impaction and suffering gastrointestinal symptoms such as abdominal pain, nausea, vomiting, unless a doctor decides otherwise. Such symptoms may indicate a possibility of ileus. Renal dysfunction patients are at risk of electrolyte imbalance. Use of products containing hydroxyanthracene glycosides by fecal impaction patients requires more frequent change of diapers in order to avoid prolonged contact of feces with skin.

Drug interactions and other interactions

Prolonged abuse of the product can result in hypokalemia, which may lead to intensification of effects of concomitantly used cardiac glycosides, antiarrhythmic medication, QT-prolonging drugs and drugs restoring sinus rhythm. Concomitant use of the product with hypokalemia-inducing medication, e.g. diuretics, corticosteroids, liquorice root, can exacerbate electrolyte deficiency.

Impact on fertility, pregnancy and lactation

No data is available on adverse or harmful effects of senna products in pregnant women or fetuses in recommended doses. Based on experimental data on genotoxicity of some anthranoids, i.a. emodin, aloe emodin, use of the product is not recommended during pregnancy. Senna products are not recommended for nursing women, due to lack of data on metabolite absorption into milk. Small amount of active metabolites (rhein) is absorbed into milk of nursing women. No laxative effect in nursed infants has been observed.

Impact on ability to drive vehicles and operate machinery

Unknown

Adverse effects

Patients with hypersensitivity to the product's ingredients may experience allergic reactions, i.a. itching, hives, rash. Cramps and abdominal pain can occur. In such cases, dosage should be lowered. Long-term use may cause dark pigmentation of the colon mucosa (pseudomelanosis coli), which usually passes upon the end of treatment. The possible metabolite pigmentation of urine (pink or red-pink, depending on pH) is not clinically significant.

Reporting suspected adverse effects

After a medicinal product receives marketing authorisation, it is important to report suspected adverse effects. It allows for continuous monitoring of the medicinal product's risk-benefit ratio. Medical professionals should report all suspected adverse effects to the Department for Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warszawa, tel.: + 48 22 49-21-301, fax: +48 22 49-21-309. Website: https://smz.ezdrowie.gov.pl.

Adverse effects can also be reported to the marketing authorisation holder.

Overdose

There may occur cramps and diarrhea with possibility of dehydration and electrolyte loss. Water and electrolyte deficiency should be balanced. Diarrhea may lead to loss of potassium ions, cardiac disorders, muscle weakness, especially with concomitant use of cardiac glycosides, diuretics, corticosteroids, liquorice root. It is recommended to monitor potassium concentration, especially in elderly patients. Prolonged overdose of anthranoids can lead to hepatitis.

PHARMACOLOGICAL PROPERTIES

Pharmacodynamics

Pharmacotherapeutic group: contact laxatives, sennosides, ATC code: A06AB06. No pharmacodynamic studies have been conducted for Senefol. 1,8 dihydroxyanthracene in senna leaves and pods exhibit laxative activity. Sennosides are not absorbed in the small intestine; sennosides are transformed into active compounds (reine anthron) in the large intestine, involving intestinal bacteria. The mode of action of sennosides is dual. They influence the large intestine peristalsis, accelerate the motility of peristaltic waves and influence intestinal secretion. The influence on intestinal secretion occurs through two coexisting mechanims. The absorption of water and electrolytes (Na⁺, Cl^–) into intestinal epithelial cells is inhibited (anti-absorption effect), leaking from tight junctions in increased, and secretion of water and electrolytes into the lumen is stimulated, increasing the fluid and electrolye content in the lumen.

Pharmacokinetics

No pharmacokinetic studies have been conducted for Senefol. Sennosides are not absorbed in the small intestine or decomposed by digestive enzymes. They are transformed into active compounds (rheinanthrone) in the large intestine, involving intestinal bacteria. Aglycone is absorbed in the small intestine. Animal trials with radiolabelled rheinanthrone administered directly to the cecum found that absorption was lower than 10%. With oxygen present, rheinanthrone oxidises to rhein and sennidins, which appear in blood, mainly in the form of glucuronides and sulphates. In case of oral use of sennosides, 3-6% of metabolites pass into urine, and some also pass into bile. Most sennosides (about 90%) are excreted in the form of polymers (poliquinones), including with undigested sennosides (2-6%), sennidins, rheinathrone and rhein. Human pharmacokinetic studies using powdered senna products (20 mg of sennosides), administered orally for 7 days, found that the maximum rhein concentration in blood was 100 ng/mL. No rhein accumulation was observed. Active metabolites, e.g. rhein, pass in small amounts into milk. Animal experimentation found small amounts of rhein permeating into the placenta.

Preclinical safety data

No preclinical trials have been conducted for Senefol.

No new systematic preclinical studies on senna leaf products have been conducted. Studies on senna pods may be considered synonymous to studies on senna leaves given the comparable composition of the herbal substances. Most of the preclinical data concerns senna pod extracts, containing 1.4-3.5% of anthranoids (potential content: 0.9-2.3% of rhein, 0.05-0.15% of aloe emodin and 0.001-0.006% of emodin) or isolated active substances, e.g. rhein or sennoside A and B.

Acute toxicity in mice and rats after oral administration of senna pods, abovementioned extracts or sennosides, was low.

In a 90-day trial, doses of 1000-1500 mg/kg of senna pods were administered to rats. The tested product contained 1.83% of sennosides A-D, corresponding to potential rhein content of 1.6%, aloe emodin content of 0.11%, and emodin content of 0.014%. All studied groups exhibited slight hyperplasia of large intestine epithelium, which reversed 8 weeks after the trial ended. The observed hyperplasia of stomach epithelium was also reversable. In case of doses of 300 mg/kg or higher, depending on the doses, an increase of basophil cells in tubules and hyperplasia of kidney epithelium were observed, with no influence on kidney function. These changes were also reversable. Dark discoloration of kidney surface, resulting from accumulation of a brown tubule pigment, persisted after recovery, although to a lesser degree. No changes in the nerve plexus of the colon were observed; the studies did not include NOEL changes (no observed effect level).

In the course of 104 one-day trials on rats of both sexes, no carcinogenic activity of orally administered doses of up to 300 mg/kg of senna pods was observed.

Sennosides did not exhibit toxicity in studies on dogs, in which doses of up to 500 mg/kg were administered for 4 weeks, nor in studies on rats, where doses of up to 100 mg/kg were administered for 6 months.

With oral administration of sennosides to rats and rabbits, no negative effect on life and development of the fetus was observed (no embryo-lethal, teratogenic, or fetotoxic effect). No effects on juvenile development, behavior of mothers nursing their young or fertility in both sexes were observed. Type of administered product is unknown.

The extract and aloe emodin exhibited mutagenicity, while sennosides A and B and rhein yielded negative results. Comparative studies of senna pods in-vivo yielded negative results.

Clinical studies on the use of senna products as laxatives and a risk factor in colorectal cancer were conducted. Some trials found a link between the use of laxatives containing anthraquinones and the occurrence of colorectal cancer, while other trials did not share these findings. It was also found that the risk is related to constipation itself and improper eating habits. Further research is necessary for definitive determination of carcinogenic risk.

PHARMACEUTICAL PARTICULARS

List of excipients

Colloidal anhydrous silica

Potato starch

Incompatibilities

No data

Expiry date

3 years

Special precautions for storage

Store closed in max. 25° C, keep away from children.

Box type and contents

Glass, polyethylene or polypropylene containers with 20, 60 or 90 tablets.

Direct packaging – PVC/Aluminum foil blister containing 10 tablets.

Outer packaging – cardboard box containing 10 tablets (1 blister) or 20 tablets (2 blisters) or 30 tablets (3 blisters) or 40 tablets (4 blisters) or 50 tablets (5 blisters) or 60 tablets (6 blisters) or 70 tablets (7 blisters) or 80 tablets (8 blisters) or 90 tablets (9 blisters) or 100 tablets (10 blisters).

Not all types of packaging need to be marketed.